Spirochaetales

SPİROCHAETALES Spirochete the word from Greek “Coiled hair”.They are long, slender, motile, flexible, undulating gram negative bacilli, that have characteristic corkscrew or helical shape.Microaerophilic, aerobic or an aerobic.Some species can be grown in laboratory culture (cell culture or tissue culture)

SPİROCHAETALES Spirochaetales Family Family Spirochaetaceae Leptospiraceaae Treponema Leptospira Borrelia
Genus
Genus


SPİROCHAETALES Treponema pallidum Syphlis. Borrelia burgdorferi Lyme disease (vector borne disease). Borrelia recurrentis Relapsing fever. Leptospira interrogans Leptospirosis (zoonoses).


SPİROCHAETALES Structural characteristics Have unique structure responsible for motility, The cell has central protoplasmic cylinder bounded by plasma membrane, enveloped by an outer membrane composed of glycolipids & lipoproteins. Between peptidoglycan & the outer sheath are located multiple periplasmic flagella, are oriented axially bundles of these endoflagella.

SPİROCHAETALES Structural characteristics

OS = outer sheath AF = axial fibrils
AF

Cross-Section of Spirochete with Periplasmic Flagella

SPİROCHAETALES


SPİROCHAETALES Histopathology showing Treponema pallidum spirochetes in testis of experimentally infected rabbit. Modified Steiner silver stain.

SPİROCHAETALES Genus

Species
Disease
Treponema Treponema Treponema Treponema
pallidum ssp. pallidum pallidum ssp. endemicum pallidum ssp. pertenue carateum
Syphilis Bejel Yaws Pinta
Borrelia Borrelia
burgdorferi recurrentis
Lyme disease (Borreliosis) Epidemic & Endemic relapsing fever
Leptospira
interrogans
Leptospirosis (Weil’s Disease)

SPİROCHAETALES Treponema pallidum Syphilis: primarily a sexually transmitted disease (venereal Treponemal Disease) Starting a small lesion (chancre). Too thin to be seen with light microscope in specimens stained with Gram stain or Giemsa. Motile spirochetes can be seen with darkfield microscopy. Staining with anti-treponemal antibodies labeled with fluorescent dyes. Intracellular pathogen.

Treponema pallidum

Can not be grown in cell cultures invitro. Do not survive well outside of host, sensitive to disinfectants, heat & drying. Transmitted from direct sexual contact or some time mother to fetus. Limited growth of the organisms, has been achieved in cultured rabbit epithelial cells. Replication is slow (generation time 30 hours).



Treponema pallidum
It secretes Hyaluronidase, an enzyme that disrupts ground substance & probably facilitates dissemination of the organism. Not have LPS or Endotoxin. Antigenic variation of surface proteins plays an important role in immune evasion.

Treponema pallidum

Virulence FactorsOuter membrane proteins promote adherence.Hyaluronidase may facilitate perivascular infiltration.Antiphagocytic coating of fibronectin.Tissue destruction & lesions are primarily result of host’s immune response (immune pathology).

Treponema pallidum

Epidemiology: Found world wide. It is the third most common sexually transmitted bacterial disease (after Chlamydia & Neisseria gonorrhoeae).

Treponema pallidum

Pathogenesis

Transmission by sexual contact or trans-placentally (congenital syphilis).

Treponema pallidum
Pathogenesis of primary syphilis The bacteria process involves invasion of mucus membranes, rapid multiplication & wide dissemination through perivascular lymphatics & systemic circulation. Primary phase is characterized by one or more skin lesions (chancres) at the site where the spirochete penetrated. It is inflammatory response at the site of inoculation resulting Chancre usually painless, changes from hard to ulcerative with profuse shedding of spirochetes. the incubation period (3-4 weeks) after initial contact.

Treponema pallidum

Pathogenesis of primary syphilis Swelling of capillary walls & regional lymph nodes. Primary lesion heals spontaneously by fibrotic walling off with in two months.

Treponema pallidum

Pathogenesis of secondary syphilis Secondary disease 2-10 weeks after primary lesions. Widely disseminated mucocutaneous rash. Secondary lesions of the skin & mucus membranes are highly contagious. Generalized immunological response.

Treponema pallidum

Pathogenesis of latent stage syphilis Following secondary disease, host enters latent period First 4 years early latent Subsequent period late latent. About 40% of the late latent patients progress to late tertiary syphilitic disease.

Treponema pallidum

Pathogenesis of Tertiary syphilis Tertiary syphilis characterized by localized granulomatous dermal lesions (gummas) in which few organisms are present. Granulomas reflect containment by the immunologic reaction of the host to chronic infections. Late neurosyphilis develops in about 1/6 untreated cases, usually more than 5 years after primary infections.

Treponema pallidum

Pathogenesis of Tertiary syphilis Central nervous system and spinal cord involvement. Dementia, seizures, wasting, Cardiovascular involvement appears 10-40 years after primary infection myocardial insufficiency and death.

Treponema pallidum

Pathogenesis of congenital syphilis Result from transplacental infection, Septicemia in the developing fetus & widespread dissemination, Abortion, neonatal mortality & late mental or physical problems.

Treponema pallidum

Clinical signs of primary syphilis Syphilitic chancre, developed at the site where the spirochete is enter to the body (inoculated). lesion start as a papule but then erodes to become a painless ulcer with raised borders. A painless regional lymphadenopathy. This ulcer heals spontaneously with in 2 months.

Treponema pallidum

Primary Syphilis


Treponema pallidum
Clinical signs of secondary syphilis A generalized mucocutaneous rash, The rash cover the entire skin surface (including the palms & soles). symptoms gradually resolve spontaneously & the patient enter the latent stage of disease.

Secondary Syphilis

Palms lesion
Soles lesion

Treponema pallidum

Clinical signs of tertiary (late) syphilis Cause a destruction of virtually any organ or tissue (arteritis, dementia, blindness). granulomatous lesions (gummas) in bone skin & other tissues. The nomenclature of late syphilis reflects the organs of primary involvement:- Neuro-syphilis Cardiovascular syphilis.

Treponema pallidum

Clinical signs of congenital syphilis In utero infections can lead to latent infections, Multiorgan malformations, or death of the fetus, Teeth and bone malformation, Blindness, Deafness Cardiovascular syphilis & rhinitis.

Congenital Syphilis

Nonvenereal Treponemal Diseases
Treponema pallidum ssp. endemicum Bejel Disease: Initial lesions: nondescript oral lesions Secondary lesions: oral papules and mucosal patches Late: gummas (granulomas) of skin, bones & nasopharynx Transmitted person-to-person by contaminated eating utensils Primitive tropical/subtropical areas (Africa, Asia & Australia)

Nonvenereal Treponemal Diseases

Treponema pallidum ssp. pertenue Yaws Disease: granulomatous disease Early: skin lesions (see below) Late: destructive lesions of skin, lymph nodes & bones Transmitted by direct contact with lesions containing abundant spirochetes Primitive tropical areas (S. America, Central Africa, SE Asia)
Papillomatous Lesions of Yaws painless nodules widely distributed over body with abundant contagious spirochetes.

Nonvenereal Treponemal Diseases

Treponema carateum Pinta Disease: primarily restricted to skin incubation period 1-3 week, Initial lesions: small pruritic papules Secondary: enlarged plaques persist for months to years Late: disseminated, recurrent hypopigmentation or depigmentation of skin lesions; scarring & disfigurement, Transmitted by direct contact with skin lesions Primitive tropical areas (Mexico, Central & South America)
Hypopigmented Skin Lesions of Pinta: depigmentation is commonly seen as a late sequel with all treponemal diseases

Laboratory Diagnosis

Microscopy Dark-field examination of the exudate from skin lesions

Laboratory Diagnosis

Microscopy Direct fluorescent antibody test Fluorescein-labeled anti-treponemal antibodies are used to stain the bacteria

Treponema pallidum in the direct fluorescent antibody test for T. pallidum.

Laboratory Diagnosis
Serology Syphilis is diagnosed in most patients on the basis of serologic tests. Two general types of tests used are biologically nonspecific (nontreponemal) tests and specific treponemal tests

Laboratory Diagnosis

Serology Nontreponemal tests (I) Measure immunoglobulin IgG and IgM antibodies (also called reaginic antibodies). Developed against lipids released from damaged cells during the early stage of disease and present on the cell surface of Treponemes. Antigen used for the nontreponemal tests is cardiolipin, which is derived from beef heart.

Laboratory Diagnosis

Serology Nontreponemal tests (II) Venereal Disease Research Laboratory (VDRL) test Rapid Plasma Reagin (RPR) VDRL test should be used to test CSF from patients with suspected neurosyphilis Nontreponemal tests develop late during the first phase of disease Serologic findings are negative in many patients who have chancres.

Laboratory Diagnosis

Serology Nontreponemal tests (III) Serologic results are positive within 3 months in all patients and remain positive in untreated patients with secondary syphilis These tests can be used to monitor the effectiveness of therapy

Laboratory Diagnosis

Serology Treponemal tests (I) Specific antibody tests used to confirm positive reactions with the VDRL or RPR tests. Fluorescent treponemal antibody-absorption (FTA-ABS) test Treponema pallidum particle agglutination (TP-PA) test

Laboratory Diagnosis

Serology Treponemal tests (II) - FTA-ABS test A fluorescent antibody test T. pallidum immobilized on glass slides is used as the antigen The slide is over layed with the patient's serum The fluorescein-labeled antihuman antibodies are then added to detect the presence of specific antibodies in the patient's serum

Laboratory Diagnosis

Serology Treponemal tests (III) Treponemal tests generally remain positive for the life of the person who has syphilis. Are influenced less by therapy than the VDRL and RPR tests.

Laboratory Diagnosis

Serology Serologic test in infants of infected mothers. A passive transfer of antibodies or a specific immunologic response to infection. Distinguished by measuring the antibody titers of the infant during a 6-month period. Undetectable levels within 3 months of birth. Remain elevated in infants who have congenital syphilis

Treatment

Long-acting benzathine penicillin for the early stages of syphilis. Penicillin G is recommended for congenital and late syphilis Tetracycline and doxycycline as alternative antibiotics for patients allergic to penicillin Only penicillin can be used for the treatment of neurosyphilis

Prevention & Control

Syphilis can be controlled only through the practice of safe-sex techniques contact. Treatment of the sex partners. Protective vaccines are not available


Clinical stages of untreated syphilis. CNS = central nervous systems.

Summary of Treponema species. 1-Indicates first-line drugs.

Borrelia Spp.
Borrelia burgdorferi (Lyme Disease) Lyme disease is caused by the spirochete B. burgdorferi, which is transmitted by the bite of a small tick of the genus Ixodes.

Genus Features• Larger spirochetes• Gram negative• Microaerophilic• Difficult to culture

Borrelia Spp.

Borrelia burgdorferi (Lyme Disease) Lyme disease characterized by three stages: Initially a unique skin lesion (erythema chronicum migrans (ECM)) with general malaise ECM not seen in all infected hosts ECM often described as bullseye rash Lesions periodically reoccur Subsequent stage seen in 5-15% of patients with neurological or cardiac involvement Third stage involves migrating episodes of non-destructive, but painful arthritis

Borrelia Spp.

Borrelia burgdorferi (Lyme Disease)

Pathogenesis: invades skin and spreads via bloodstream to involve primarily the heart, joints, and CNS; arthritis is caused by immune complexes.
Clinical stages of untreated Lyme disease. CNS = central nervous system.



Borrelia Spp.
Borrelia burgdorferi (Lyme Disease)

Diagnosis: Serodiagnosis by ELISA (negative early); Western blot for confimation. Treatment: Doxycycline, amoxicillin, or azithromycin/clarithromycin for primary; Ceftriaxone for secondary; Doxycycline or ceftriaxone for arthritis Prevention: DEET; avoid tick bites; vaccine (OspA flagellar antigen) not used in U.S.

Borrelia Spp.

Borrelia recurrentis (Relapsing Fever)
Epidemiology Arthropod vectors Louse-borne borreliosis = Epidemic Relapsing Fever Transmitted person-to-person by human body lice (vectors) from infected human reservoir Infect host only when louse is injured, e.g., during scratching Therefore, a single louse can only infect a single person Lice leave host that develops a fever and seek normal temperature host Tick-borne borreliosis = Endemic Relapsing Fever Sporadic cases Transmitted by soft body ticks (vectors) from small mammal reservoir Ticks can multiply and infect new human hosts

Borrelia Spp.

Borrelia recurrentis (Relapsing Fever)
Pathogenesis Antigenic variation leads to return of fever/chills Diseases Relapsing fever (tick-borne relapsing fever in U.S. is caused mainly by B. hermsi); associated with camping in rural areas of Colorado. Diagnosis Spirochetes seen on dark-fi ld microscopy of blood smear when patient is febrile Treatment: doxycycline

Borrelia Spp.

Leptospira interrogans.
Leptospirosis (Weil’s Disease) Reservoir: wild and domestic animals (zoonosis) Obligate aerobes, Characteristic hooked ends (like a question mark).
Silver Stain of Leptospira interrogans


Leptospira interrogans.
Leptospirosis (Weil’s Disease) Epidemiology A zoonotic disease Transmitted to humans from a variety of wild and domesticated animal hosts Transmitted through breaks in the skin or intact mucus membranes Indirect contact (soil, water, feed) with infected urine from an animal with leptospiruria

Leptospira interrogans.

Leptospirosis (Weil’s Disease) PathogenesisLeptospirosis, also called Weil’s disease in humansDirect invasion and replication in tissuesCharacterized by an acute febrile jaundice & immune complex glomerulonephritisHepatic injury & meningeal irritation is commonIncubation period usually 10-12 days with flu-like illness usually progressing through two clinical stages:-Leptospiremia develops rapidly after infection (usually lasts about 7 days) without local lesionInfects the kidneys and organisms are shed in the urine (leptospiruria) with renal failure and death not uncommon

Leptospira interrogans.

Leptospirosis (Weil’s Disease) Clinical Syndromes(Anicteric leptospirosis) Systemic with aseptic meningitis(Icteric leptospirosis) Overwhelming disease (Weil’s disease) Vascular collapseThrombocytopeniaHemorrhageHepatic and renal dysfunctionNOTE: Icteric refers to jaundice (yellowing of skin and mucus membranes by deposition of bile) and liver involvement.

Leptospira interrogans.

Leptospirosis (Weil’s Disease) Diagnosis: Serodiagnosis (agglutination test); culture (blood, CSF, urine) available in few labs; dark-fi ld microscopy insensitive. Treatment: Penicillin G or doxycycline. Prevention: Doxycycline for short-term exposure; vaccination of domestic livestock and pets; rat control

Leptospira interrogans

Leptospirosis (Weil’s Disease)